Tumor is the main lethal type of major diseases that human beings are facing nowadays. Traditional therapies, such as chemotherapy, surgery, radiotherapy, etc, have been the mainstay of tumor treatment for a long time, and still have their own limitations in terms of effectiveness. In recent years, immunotherapy for tumors has attracted much attention with the rise of strategies such as immune checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) relay therapy, and anti-tumor vaccines. Among them, CAR-T cell therapy, as a breakthrough tumor immunotherapy method, can precisely target tumors at the cellular and molecular levels by modifying the patient’s own T cells to express recombinant antigen receptors targeting specific tumor antigens, breaking the restriction of the major histocompatibility complex (MHC) of the natural T cells themselves. It can precisely target tumors at the cellular and molecular levels, and thus can efficiently and specifically identify and kill cancer cells, providing a new perspective for treatment. Since the approval of the first CAR-T therapy by the US Food and Drug Administration (FDA) in 2017, in addition to still maintaining significant advantages in the field of classical multiple hematologic malignancies, it has also made outstanding progress in the treatment and clinical trials of some solid tumors and autoimmune diseases, among others. This paper  will briefly review the current principles, applications, challenges and directions of development of CAR-T technology. 

With the rapid development of the Internet, the problem of internet gaming disorder (IGD) among adolescents has gradually become prominent. IGD has caused serious harm to their physical and mental health, and it is difficult to withdraw and treat. In 2019, the World Health Organization (WHO) officially listed Gaming Disorder (GD) in the diagnostic category and included it in the 11th edition of the International Classification of Diseases. In China, the number of adolescent internet users has approached 200 million, and the number of IGD patients is relatively large. It is urgent to make breakthroughs in the cognition and treatment of IGD. Domestic and foreign studies have shown that IGD’s physical and psychological harm to adolescents is related to the abnormal activation and functional connection damage of structures such as the prefrontal lobe, limbic system, and striatum, which in turn causes neurocognitive disorders, executive dysfunction, difficulty in emotional regulation, abnormal reward and punishment feedback, behavioral abnormalities and other functional disorders; therefore, this article aims to systematically review the research literature on IGD in recent years, and use neurophysiological imaging research method  to sort out the changes in the brain structure and function of adolescents with IGD, in order to improve the understanding of the pathophysiology of the disease, and assist in further clinical diagnosis, treatment, application and research design. 

Objective To explore whether creatine therapy regulates neuronal ferroptosis by inhibiting the activation of STAT1 signaling pathway associated with suppressor of cytokine signaling 1 (SOCS1) in Alzheimer’s disease.   Methods  Immunohistochemical staining and counting of positive results using paraffin sections of human brain frontal lobes were employed to determine the trend of changes in the target proteins. Further validation was performed by immunofluorescence and Western blotting. STAT1 phosphorylation was inhibited by creatine injection using eleven FAD4Tmice and by cerebellar medullary pool puncture, and the expression of target proteins was examined by immunohistochemistry and immunofluorescence after postmortem sampling.   Results  Compared with the age controls, interferon-γ (IFN-γ), an activating cytokine of the STAT1 signaling pathway, and SOCS1, a negative regulator of STAT1 activation, were both significantly up-regulated, STAT1 phosphorylation was enhanced, and the ferroptosis markers ferritin light chain (FTL) and cystine/glutamate transporter(xCT) increased markedly in the cortex of AD human brains; Creatine treatment of FAD4Tmice resulted in a reduction of both IFN-γ and SOCS1, and a significant decrease in the ferroptosis markers FTL and xCT (SLC7A11).  Conclusion  Creatine ameliorates neuronal ferroptosis in AD model mice by reducing neuronal STAT1SOCS1 signalling activation. 

Objective  To explore an experimental protocol for differentiating humaninduced pluripotent stem cells (iPSCs) into highly pure midbrain dopaminergic (DA) neurons.    Methods  By optimizing a blend of small molecules and recombinant human growth factors, iPSCs were induced to differentiate into ventral midbrain floor plate DA progenitor cells and subsequently into mature substantia nigra pars compacta DA neurons. Throughout the differentiation process, Real-time PCR and immunofluorescent staining were utilized as a method  for quality assessment. Results  iPSCs firstly differentiate into dopaminergic precursor cells, and then gradually differentiate into DA neurons expressing tyrosine hydroxylase (TH).     Conclusion  The protocol successfully yields approximately high purity tyrosine hydroxylase-positive (TH+) DA neurons. This differentiation technique offers an effective cellular model for studying the physiological mechanisms and pathogenesis of Parkinson’s disease, providing valuable insights for future research and potential therapeutic strategies. 

Objective To investigate gender differences and age-related changes in body composition(BC) among Miao adults in Rongshui, Guangxi Province, and to provide the basis for assessing nutritional status and health.   Methods  With informed consent, 630 Miao adults (218 males, 412 females) were randomly selected for this study. Body composition was assessed using bioelectrical impedance analysis(BIA).   Results  Weight, fat-free mass, muscle mass, trunk muscle mass, limb muscle mass, waist-to-hip ratio(WHR), body water, presumtion of bone mass and protein were significantly higher in males than in females. And the fat mass, trunk fat mass, limb fat mass, visceral fat content, subcutaneous fat content and percentage of body fat were significantly higher in females than in males. According to the evaluation of body mass index(BMI) and WHR, the proportion of overweight and obesity of Miao adults was higher than the average level of Miao residents, and their obesity was characterized by central obesity. With age, weight, fat mass, muscle mass, fat-free mass, limb muscle mass, limb fat mass, subcutaneous fat content, percentage of body fat, body water, presumtion of bone mass, and protein of Rongshui Miao adults showed a gradual decreasing trend, while visceral fat content and WHR increased progressively. BMI in male Miao adults, along with BMI, fat mass, trunk fat mass, subcutaneous fat content, percentage of body fat, and body water in female Miao adults, showed a trend of increasing followed by decreasing, peaking at the age of 40-49  years.    Conclusion  The body composition of Miao adults in Rongshui, Guangxi, exhibits significant gender differences and age-related variation change patterns, which may increase the risk of sarcopenia and metabolic diseases with aging.  

Objective To investigate the effect and mechanism of hypoxia inducible factor-1α/aquaporin-4 (HIF-1α / AQP4) pathway in high altitude cerebral edema (HACE) after blood-brain barrier injury in rats.  Methods  Adult male SD rats (n= 40) were randomly divided into two groups: control group (Ctrl, n= 20) and high altitude cerebral edema group (HACE, n= 20). The rats in the control group were reared in Xining (altitude 2261m) for 4 days, and the rats in HACE group were reared in low-pressure simulation chamber (altitude 5000m) for 4 days. Brain water content was measured by the method  of dry and wet weight. The intracranial structure, morphology and signal changes of small animals were observed through T2 weighted image of 7.0 T MRI. The morphological changes of neurons and the apoptosis of nerve cells in the CA1 region of hippocampal tissue were observed by the staining of Nissl and TUNEL. Immunohistochemical staining was performed to observe the extravasation of immunoglobulin G (IgG). The expressions of HIF-1α, AQP4, matrix metalloproteinase-9 (MMP-9), claudin-5, occludin and zonula occludens-1（ZO-1）in the tissue of hippocampal were detected by the method  of Western blotting and immunofluorescent staining.  Results  The brain water content increased significantly in the HACE group (P < 0.05). The neurons in CA1 region of hippocampal tissue were atrophic and deformed, the arrangement of neurons was disordered in the HACE group. The number of neurons decreased significantly, the apoptosis of nerve cells increased significantly, and the IgG exudates obviously in the CA1 region of hippocampal tissue in the HACE group. The expressions of HIF-1α, AQP4 and MMP-9 proteins increased significantly, while claudin-5, occludin and ZO-1 proteins decreased significantly in the CA1 region of hippocampal tissue, which detected by the method  of Western blotting and immunofluorescent staining (P<0.05).  Conclusion  Acute high-altitude hypoxia can induce to blood-brain barrier disruption through the HIF-1α/AQP4 pathway, resulting in high-altitude cerebral edema. 

Objective  To investigate the types and mechanisms of microglial cell death induced by interaction between palmitic acid (PA) and lipopolysaccharide (LPS).  Methods  BV-2 microglial cells were divided into three groups for apoptosis research, BSA group, PA treatment group, and staurosporine (STA) group. They were further divided into four groups for necrosis research, BSA group, BSA + inhibitor group, PA group, and PA + inhibitor group. Western blotting was conducted to assess the expression levels of key proteins involved in apoptosis and necrosis pathways. The effect of PA on microglial cells was validated through feeding a high-fat diet to Institute of Cancer Research(ICR) mice. Results  Apoptotic microglia were observed in both BSA group and PA group, PA significantly induced the activation of caspase-3, caspase-7, and poly ADP-ribose polymerase(PARP). However, compared to the BSA group, the level of activated Caspase-7 in the STA group did not change significantly. Inhibition of ferroptosis, necroptosis, or autophagy did not protect against PA-induced cell damage, while the Caspase-11 inhibitor, wedelolactone (WE), significantly improved PA induced cell damage. This study also found that PA could promote LPS entry into microglial cells and induce pyroptosis. This phenomenon and the protective effect of WE were further confirmed in a high-fat diet mouse model through immunofluorescent staining and Western blotting.   Conclusion  PA induces apoptosis and pyroptosis in microglial cells, while simultaneously promoting LPS entry into microglial cells and inducing pyroptosis.

 In recent years, more and more researches has focused on the correlation between cognitive activity and physiological variables. The change of pupil is regarded as an important target in the cognitive process, and has become a hot research field. This review focuses on the three key brain regions that regulate pupil change, and reflects the neurophysiological mechanism behind pupil change by elaborating the neural pathways related to pupil change and cognitive performance. Based on recent studies on pupil change in cognitive diseases, it aims to promote the application of pupil change in the field of cognitive science in the future. 

Objective  To explore the neuroprotective effects and mechanisms of the sesquiterpene lactone compound ACT001 on rotenone (ROT) -induced Parkinson’s disease (PD) model mouse.  Methods  SPF C57BL/6 mice were randomly divided into 6 groups, including control group, solvent control group, ROT model group, ACT001 5 mg/kg group（ROT+ACT001-5）, ACT001 20 mg/kg group（ROT+ACT001-20）, and levodopa(L-dopa) positive control group(ROT+L-dopa)，with 9 mice in each group. The control group received an equivalent amount of intraperitoneal injection of saline, the solvent control group received an equivalent amount of rotenone solvent without rotenone, the remaining groups of mice were used to establish a PD mouse model by intraperitoneal injection of rotenone. Mice in different ACT001 dosage groups received intraperitoneal injections of high and low doses of ACT001, while the positive control group received levodopa intraperitoneally for 15 consecutive days. Behavioral changes in mice were assessed using open field, rotarod, pole-climbing, and balance beam tests. Immunofluorescence (IF) assay to detect the expression of tyrosine hydroxylase (TH) neurons，content of TH-positive fibers in the striatum and to detect the activation status of nigrostriatal microglia in the mouse midbrain; Real-time PCR was employed to measure the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) in the substantia nigra of the mouse brain. Western blotting was used to measure the protein levels of TH, nuclear factor-κB (NF-κB) p65, NF-κB inhibitor α (IκBα), and phosphorylated IκBα (p-IκBα) in the substantia nigra of the mouse brain.  Results  Compared to the control group and the solvent control group, the rotenone-induced PD model group exhibited motor impairments in behavioral tests, a decrease in the number of TH positive neurons in the substantia nigra (P <0.0001), decreased levels of TH-positive fibers in the striatum, activation of midbrain substantia microglia，and elevated levels of IL-6,  IL-1β, TNF-α, p-IκBα, and NF-κB p65 expression. ACT001 significantly improved the behavioral impairments and substantia nigra damage in PD mice, increased the number of TH-positive neurons in the substantia nigra, increased levels of TH-positive fibers in the striatum, inhibition of microglial cell activation in the midbrain substantia nigra, and elevated the protein expression levels of IκBα while reducing the levels of IL-6, IL-1β, TNFα, -IκBα, and NF-κB p65 in the substantia nigra ( P<0.05). At a dose of 5 mg/kg, ACT001 significantly improved behavioral impairments in rotenone-induced PD mice, reduced the loss of dopaminergic neurons, and its mechanism may be related to the inhibition of the NF-κB  signaling pathway and the suppression of inflammation. In summary, the intervention of ACT001 in the rotenone-induced PD mouse model inhibited the inflammatory response in the midbrain, increased the number of TH-positive neurons, and augmented the population of dopaminergic neurons in the substantia nigra, exerting a protective effect on neurons.   Conclusion  ACT001 significantly improves behavioral deficits in ROT-induced PD mice, ameliorates of dopaminergic neuron loss from the midbrain substantia nigra and striatum, inhibits the activation of nigrostriatal microglia in the midbrain, and suppresses inflammatory responses by inhibiting the activation of the NF-κB signaling pathway. 

Objective To investigate the mechanism of hippocampal neuronal plasticity of newborn neurons in the hippocampus by which exercise improves the fear and anxiety symptoms of post-traumatic stress disorder (PTSD).   Methods Totally 40 C57BL/6J male mice were randomly divided into by control group (Ctrl) and PTSD group, the PTSD group was divided into a no-exercise group (PTSD), a low-intensity exercise group (L) and a high-intensity exercise group (H). The PTSD model mice were constructed by combining conditioned plantar-foot shock (CF) and single-session sustained stress (SPS). After the exercise intervention, the fear and anxiety levels of the mice were assessed using the conditioned fear test and the elevated cross maze test; Subsequently, the densities of the newborn mature neurons in dentate gyrus(DG) of hippocampus were detected by immunofluorescent double-labelling staining, and the newborn neuron morphology was marked by injecting retrovirus pRetro-U6-EF1-EGFP-3xFLAG-WPRE in DG of hippocampus to observe its morphology. The morphology of the newborn neurons was labelled to observe their dendritic length and the number of branch points; Meanwhile, the concentration level of adiponctin(APN) in the hippocampal area was determined by ELISA.  Results The result  showed that both high and low-intensity exercise interventions significantly reduced the freezing time of PTSD mice in the conditioned fear test, and in the elevated cross maze experiment, the residence time and the number of entries in the open arm of the mice in the H group increased significantly compared with those in the PTSD group, while the residence time and the number of entries in the closed arm were significantly reduced. In addition, both high and low-intensity exercise interventions significantly increased the surface density and dendritic length of newborn mature neurons in the hippocampal DG region of PTSD mice, and high-intensity exercise significantly increased the number of dendritic branching points, and the density of newborn mature neurons in the H group was more significantly increased compared with that in the L group. At the same time, the hippocampal APN concentration increased significantly in both L and H groups compared with the PTSD group, and it was more significant in the H group.  Conclusion Exercises have an ameliorative effect on anxiety and fear symptoms in PTSD mice, and at the same time, it can increase hippocampal neuroplasticity and adiponctin secretion in PTSD mice, suggesting that the improvement of fear and anxiety symptoms in PTSD by exercise may be related to the increase of hippocampal neuroplasticity and APN secretion, and the improvement effect is better with high-intensity exercise.

 Objective  To investigate the effects of short-term and long-term high-fructose diets on hippocampal neurometabolites and anxiety and depression-like behaviors in mice, revealing the potential mechanisms of high-fructose diets in mood disorders and providing a experimental basis for the prevention and treatment of related diseases.  Methods C57BL/6J male mice were randomly divided into two groups, control group (standard diet, n=10) and experimental group (high-fructose diet, n=10). Four weeks (short-term) and eight weeks (long-term) later, each group of mice was examined for body weight and fasting blood glucose, and neurometabolites levels in the hippocampus were detected by hydrogen proton magnetic resonance spectroscopy(1H-MRS), followed by the open-field test, the forced-swimming test, and the tail-suspension test to evaluate anxiety-like and depression-like behaviors.   Results  High fructose diet for 4 weeks elevated glutamate levels and reduced glutathione and myo-inositol levels in mice, accompanied by shortened immobility time in the forced swim test. High fructose diet for 8 weeks not only led to abnormalities in body weight and glucose metabolism but also caused a reversal decrease in hippocampal glutamate levels and induced significant anxiety-like behaviors, and the decrease in hippocampal glutamate levels showed a significant negative correlation with the enhancement of anxiety-like behaviors.   Conclusion   Altered hippocampal glutamate levels may be a key contributing factor to the anxiety-like behaviors induced by long-term high-fructose diet.

Objective  To explore the anatomical landmarks and segmentation method  for the intraoperative identification of the cervical segment of the internal carotid artery by studying cadaveric dissections with an endoscopic transoral medial pterygomandibular fold approach and to investigate its clinical significance.   Methods  The head specimens of five fresh frozen cadavers were dissected in the anatomical laboratory of the Surgical Treatment Technology Innovation Unit of Nasal Skull Base Tumor in Eye & ENT Hospital of Fudan University. The parapharyngeal space was dissected layer by layer through the endoscopic transoral medial pterygomandibular fold approach, and the location marks of parapharyngeal internal carotid artery (ppICA) and adjacent structures of ppICA were anatomically studied. The anatomical landmarks associated with ppICA were observed and characterized, and the ppICA was segmented anatomically according to its adjacent structures. Then, the length of each ppICA segment was measured.  Results  Muscle structures were essential anatomical landmarks for an endoscopic transoral pterygoid medial approach that identifies mandibular folds. The first layer of muscles included the superior pharyngeal constrictor, tensor veli palatini, and medial pterygoid muscles. The second layer includes the stylopharyngeus, styloglossus, longus capitis, and levator veli palatini muscles. The stylopharyngeal and levator veli palatini muscles were close to the ppICA and were reliable landmarks for locating the ppICA. Furthermore, the ppICA was divided into three segments according to their positional relationship with the ppICA. The first segment of ppICA(P1ICA) was located between the greater horn plane of the hyoid bone and the intersection plane between the upper margin of stylopharyngeal muscle and ppICA. The second segment of ppICA (P2ICA) was between the plane where the upper edge of the stylopharyngeal muscle intersected with the ppICA and the plane where the projection of inferior edge of the levator veli palatini muscle intersected with the ppICA. The third segment of ppICA (P3ICA) was between the intersection of the lower margin projection of the levator veli palatini muscle and ppICA and the external orifice of the carotid canal. The P2ICA was within an anatomical region bounded by the levator veli palatini muscle, longus capitis muscle, and stylopharyngeus muscle. This region was termed “ICA window” in this paper measured under the cadaver head specimen, the lengths of P1ICA, P2ICA, and P3ICA were (36.5±7.3) mm, (15.5±1.6) mm, (7.4±1.7) mm respectively.   Conclusion  The muscular structure refers to the relatively constant anatomical reference landmarks within the endoscopic transoral medial pterygomandibular fold. The stylopharyngeus and levator veli palatini muscles are reliable landmarks for precisely locating and segmenting the ppICA, thus having essential clinical implications.  

Objective To investigate the effects of peripheral blood neutrophil infiltration on the polarization regulation of cerebral resident microglia under a permanent ischemic stroke model.    Methods  Fifty-eight C57BL/6 mice were divided into two groups. One group was sham group, and the other group of mice was subjected to permanent middle cerebral artery occlusion surgery. Mice were euthanized 48 hours, 7 days, 14 days, and 30 days after surgery for tissue collection. Western blotting was used to detect expression levels of M1 microglia markers CD16, M2 microglia marker arginase 1(Arg1), inflammatory cytokine interleukin-1β (IL-1β), and neutrophil marker myeloperoxidase (MPO) in brain tissue. Immunofluorescence histochemical staining was used to assess neutrophil infiltration and M2 microglial distribution around the infarct area in brain sections. In vitro, purified neutrophils were co-cultured with BV2 microglial cells. After lipopolysaccharide stimulation, the phagocytosis of neutrophils by BV2 cells was observed, and the expression levels of CD16 and Arg1 proteins in BV2 cells were detected.    Results Western blotting showed that the levels of CD16 (P<0.05), IL-1β (P<0.001), and MPO (P<0.05) in brain tissue increased significantly 48 hours and 7 days after surgery, then decreased, with MPO expression returning to normal levels 30 days after surgery. Immunofluorescence showed a significant increase of MPO-positive cells around the infarct area of the mouse cerebral cortex 48 hours after surgery (P<0.001), followed by a decrease (P<0.05). The number of ionized calcium binding adapter molecule 1 (Iba1) and MPO double-positive cells gradually increased after surgery,  and reached their peak at 14 days (P<0.05). Iba1 and Arg1 double-positive cells also increased significantly 7 days (P<0.05) and 14 days (P<0.01) after surgery. In vitro, co-culture experiments showed that after BV2 phagocytosing neutrophils, CD16 (P<0.05) significantly decreased and Arg1 significantly upregulated (P<0.05).    Conclusion  In a permanent ischemic stroke model, microglia transition from M1 to M2 type after phagocytosing neutrophils, and the injured brain area changes from pro-inflammatory state to anti-inflammatory state. 

 The metabolic enzyme fructose-1,6-bisphosphatase 1 (FBP1) plays an important role in tumour development. In a variety of tumors, the high expression level of FBP1 has been correlated with a good prognosis. FBP1 can regulate the tumor cell metabolism reprograming by inhibiting glycolysis and fat metabolism, play the roles of protein phosphatase by regulating the NF-κB pathway and block tumor progression by regulating tumour immune cell infiltration. However, FBP1 promote malignant progression in a few tumors, some of the regulatory mechanisms are still unclear and need to be followed up with further research. 

 

Bone metastasis is a pathological condition in which malignant tumors originating from non-osseous tissues disseminate to bone tissue via the bloodstream, lymphatic system, or direct infiltration,  inducing  bone destruction and severe pain. This condition disrupts normal bone metabolism and triggers various skeletal-related events (SREs), thereby significantly impairing patients’ quality of life. Current therapeutic strategies for bone metastasis include surgical intervention, radiotherapy, targeted therapy, and immunotherapy. Among these, bone-targeted therapy has shown promising potential in managing bone metastasis. Recent advancements have highlighted osteoblasts and osteoclasts, the primary regulators of bone remodeling, as critical therapeutic targets. Consequently, several bone-targeted drugs have been developed. These agents not only substantially reduce the incidence of SREs but also markedly enhance patients’quality of life and clinical outcomes. In this review, we elucidate the mechanisms of drug action targeting osteoclasts and osteoblasts, and propose potential directions for future research in bone-targeted therapy. 

Facing of mounting resource constraints and rising demands for personalization in medical education, regional anatomy teaching urgently requires transformation. In this paper, we focus on the regional anatomy of the thoracic wall, in order to explore a novel AI-driven teaching paradigm. Anchored in the core principle of “virtual-real integration with cadaveric dissection as the cornerstone,” the paradigm redefines educational objective  and constructs an intelligent, closed-loop teaching model integrating students, computers, and instructors. Leveraging the robust support of digital intelligence (e.g. , DeepSeek), this paradigm incorporates interactive method including group collaboration, branching instruction, and gamified assessments. It achieves a comprehensive intelligent transformation of the entire teaching process—from goal setting and plan customization to activity implementation, task completion, outcome exchange, multidimensional evaluation, and reflective iteration. This new paradigm centers on medical students and leverages digital intelligence to activate deep personalized learning potential. It seamlessly integrates fundamental anatomical knowledge with clinical scenarios (e.g. , key anatomy in breast cancer surgery, flap design in breast reconstruction), and significantly enhances clinical decision-making abilities, scientific research and innovative thinking, as well as medical humanistic literacy, paving a new path for intelligent medical education.

Objective To study the mandibular characteristics of the modern population in Beijing region. Methods  In this study, we examined 22 measurements and their sexual dimorphism index (SDI) of 193 adult mandibles (126 males, 67 females) collected from the Beijing region. In addition, eight mandibular indexes were calculated. These mandibular dimensions of the Beijing population were compared with those of other modern and contemporary populations in Asia, as well as Neolithic-historical populations in Northern China. Results  The predominant mandibular index in the contemporary Beijing population was dolichostenomandibular. The SDI of mandibular size exhibited a wide range of variation. It was noteworthy the minimum height of mandibular ramus, height of mandibular ramus, height of coronoid process and minimum breadth of mandibular ramus demonstrate significant sexual dimorphism (SDI ≥10%). The mandibular size aligned with the variation range of modern and contemporary Asian populations, with the cluster analysis indicating an affiliation with Northern Mongoloids. But the Beijing population was far away from other Northern populations in China. The mandibular size was more gracile compared to ancient populations in Northern China, whereas the height of mandibular ramus was greater than those of the latter. Conclusion  This study provides valuable insights into the physical characteristics of modern populations in Beijing region.

Objective To develop a method  of combining electroencephalogram(EEG) /electromyography (EMG) with multi-regional fiber photometry recording to simultaneously capture the changes of neuronal activity in the whole brain and specific brain regions during epileptic seizures.    Methods The mouse head was divided into left and right regions based on the middle suture of the skull. EEG electrodes (EEG/EMG) were implanted in one side, while optical fibers were implanted in the striatum, hippocampus, entorhinal cortex, and thalamus on the contralateral side to simultaneously monitor EEG, EMG, and calcium signal dynamics.    Results By combining EEG/EMG with multi-regional fiber photometry recording, differences in neuronal activity across brain regions, alongside EEG and EMG, were observed during different behavioral states. In a kainic acid (KA)-induced epilepsy model, abnormal synchronous neuronal discharges in the mouse brain were accompanied by calcium signal changes in the striatum, hippocampus, entorhinal cortex, and thalamus, with the earliest changes occurring in the hippocampus.    Conclusion The combined use of EEG/EMG and multi-brain-region fiber photometry is successfully implemented in mice. This method  synchronously recordes abnormal calcium signal changes across multiple brain regions, along with EEG and EMG, in the KA-induced epilepsy model.  

Objective To explore the pathogenesis of Alzheimer’s disease by examining the effects of dihydroartemisinin(DHA) on cognitive behavior, hippocampal, cerebral cortex and retinal cell morphology, β-amyloid(Aβ) and autophagy-related proteins in 5×FAD mice.   Methods  Twenty 5×FAD mice and 5 wild type (WT) mice were selected, all of which were female. The 5×FAD mice were randomly divided into model (M) group, donepezil (D) group, low-dose DHA (DHA-L) group, and high-dose DHA (DHA-H) group. The WT and M groups were not treated, and the D group was given donepezil 0.1 mg/kg per day. DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day, respectively. Group D, group DHA-L and group DHA-H were given intragastric administration once a day for 3 months. The changes of in cognitive behavior were measured by Morris experiment. HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex, hippocampus and retina. The expressions of Aβ protein in cerebral cortex, hippocampus and retina were detected by immunohistochemistry. Western blotting detected the expression of autophagy related proteins (LC3-Ⅰ, LC3-Ⅱ, Beclin-1, P62, β-actin).   Results  The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes. Compared to the model group, significant differences in the contents of Aβ  in the hippocampal CA1, cerebral cortex S1, and retinal were observed (P<0.0001) in the other four groups. The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,  DHA-H, and model groups (P<0.01).  Conclusion  DHA improves cognitive function and increases the number of nerve cells in mice. It also reduces Aβ content in the cerebral cortex, hippocampus, and retina, along with improving autophagy-associated protein deposition in mice.  

Objective  To investigate the effect of up-regulating tumor necrosis factor alpha induced protein 3 (TNFAIP3) expression on hippocampal neurons in mice with cerebral ischemia-reperfusion.    Methods  The mice were randomly divided into 6 groups: sham group, sham empty vector group (sham-), sham TNFAIP3 high expression group (sham+), model group, model empty vector group (model- ), model TNFAIP3 high expression group (model+ ). A mouse model of middle cerebral artery occlusion and cerebral ischemia-reperfusion was established using the suture method. After the successful establishment of the model, lentivirus was injected into the hippocampus 24 hours later. Two weeks later, samples were collected and Western blotting was used to detect the expressions of TNFAIP3 and ERK signaling pathway proteins. The changes in ischemic area were observed by 2,3,5-triphenyltetrazolium chloride (TTC) staining; HE staining was used to observe the morphological changes of hippocampal neurons, and ELISA was used to detect the expressions of lipoprotein-associated phospholipase A2 (Lp-PLA2) and interleukin (IL)-8.     Results  The results of Western blotting indicated that the TNFAIP3 expression in the model group decreased significantly compared with the sham group (P<0.05); Compared with the model group, there was no significant change in TNFAIP3 expression in the model-  group (P>0.05); The TNFAIP3 expression in the model+  group increased significantly compared with the model group and model-  group(P<0.05). Compared with the sham group, the results of the sham+  group showed that the ischemic area had no significant changes in TTC staining, and there were no significant changes in hippocampal neuronal morphology, and the expressions ERK signaling pathway proteins, Lp-PLA2 and IL-8 (P>0.05); Compared with the sham-  and sham+  groups, the model group showed an increase in ischemic area, significant damage to hippocampal neurons, a decrease in the number of Nissl bodies, and a significant increase in the expressions of ERK signaling pathway proteins, Lp-PLA2, and IL-8 (P<0.05); Compared to the model-  group, the model+  group showed a decrease in ischemic area, an increase in the number of neurons in the hippocampus and the number of Nissl bodies, and a significant decrease in the expressions of ERK signaling pathway proteins, Lp-PLA2, and I-8 (P<0.05).   Conclusion  Up-regulation of TNFAIP3 may be one of the methods for repairing hippocampal neuronal damage caused by cerebral ischemia reperfusion.

Objective  To explore the behavioral patterns and hippocampal neurogenesis of CHD8^+/- mice, and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.   Methods  Genotype of wild type (WT) and CHD8^+/- mice was identified. Weight measurement was conducted on both male and female mice of the WT and CHD8^+/- strains. Subsequently, a battery of behavioral tests was administered, which included three-chamber test, self-grooming test, nesting test, Y-maze spontaneous alternation test,  food burial test, open-field test and light-dark transition test. Afterwards, the mice were administered 2% pentobarbital sodium (2 ml/kg) to induce anesthesia. Their brains were frozen with 4% paraformaldehyde, removed for photography and analysis to identify any alterations in brain size. Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.   Results  Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8 (CHD8) protein in both male and female mice with CHD8^+/- genotype, as compared to WT mice. There were no notable disparities in body weight between male and female WT and CHD8^+/- mice, as well as in brain size. The three-chamber social behavior test revealed that both male and female CHD8^+/- mice had social deficiencies (P<0.05). During the open field test, there was no significant difference in the total distance moved by male and female WT and CHD8^+/- mice. However, the amount of time spent in the central region was considerably lower in CHD8^+/- mice compared to the WT mice (P<0.01). Furthermore, the light-dark transition test revealed that both male and female CHD^8+/- mice spent considerably less time investigating the white box compared to the WT mice (P<0.05). Nevertheless, there were no notable alterations found in self-grooming, nesting, spontaneous alternation of Y-maze, and food burial experiments. In addition, Western blotting result  demonstrated a significant drop in doublecortin (DCX) expression (P<0.001), and immunofluorescent staining revealed a notable reduction in the number of DCX⁺ cells (P<0.01) in the hippocampus of CHD8^+/- mice.   Conclusion  CHD8^+/- mice exhibit social disorders and anxiety-like behaviors, with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders. 

 Objective To evaluate the changes in postoperative plasma β-endorphin(β-EP) levels in patients who had received perioperative electroacupuncture（EA） treatment in 10 randomized controlled trials (RCTs) and examine the impact of EA on postoperative pain.   Methods  This meta-analysis evaluated the changes in plasma β-EP levels and visual analog scale (VAS) 12, 24 and 48 hours after surgery in patients receiving perioperative EA. It also assessed the changes in plasma serotonin (5-hydroxytryptamine, 5-HT) and prostaglandin E2 (PGE2) levels at 24 hours postsurgery. A comprehensive search was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang, Chongqing VIP database, Chinese Biomedical Database (CBM), Web of Science, and PubMed databases. RCTs on perioperative EA and β-EP published from the inception of the websites up to July 25, 2023, were retrieved. Effect size aggregation, literature quality assessment, and bias analysis were performed using RevMan 5.3 software, and sensitivity analysis was conducted via R 4.3.1.   Results  A total of 10 RCTs involving 706 patients were included. EA in conjunction with conventional anesthesia significantly increased plasma β-EP levels at 12 hours postsurgery ［standard mean difference (SMD)=2.79, 95% CI (1.85, 3.72), Z=5.81, P<0.00001］, 24 hours postsurgery ［SMD=1.87, 95% CI (0.9, 2.83), Z=3.79, P=0.0001］, and 48 hours postsurgery ［SMD=2.02, 95% CI (1.49, 2.54), Z=7.50, P<0.00001］. EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery, and the VAS at 12, 24 and 48 hours after surgery also decreased.   Conclusion  These findings suggest that perioperative EA markedly elevates plasma β-EP levels, reduces pain-inducing factors in plasma, and effectively alleviates acute postoperative pain.

Objective To explore the role of the protein kinase R-like endoplasmic reticulum kinase (PERK)-mediated endoplasmic reticulum stress pathway in a model of lipopolysaccharide(LPS)-induced microglia inflammation.   Methods  To investigate its effects on endoplasmic reticulum (ER) stress, an inflammation model of microglia was established by stimulating with LPS at gradient concentrations for 24 hours and with 1 mg/L LPS for different durations. Cell viability was assessed by the CCK-8 assay; The mRNA and protein expression levels of related inflammatory factors were measured by Real-time PCR and ELISA kits. Cellular oxidative stress was evaluated by detecting reactive oxygen species (ROS), and Realtime PCR and Western blotting were used to examine the mRNA and protein expression levels of ER stress pathway markers associated with inflammation.   Results  1. The effects of different concentrations of LPS on cell viability and morphology were not statistically significant after acting on BV-2 cells for 24 hours (P>0.05); 2. 1 mg/L LPS incubated with BV-2 cells for different times and the cell viability decreased with the increase of time; 3. Compared with the 0 hour group, the levels of pro-inflammatory cytokine interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) mRNA and protein expression increased significantly (P<0.05) in the LPS-stimulated 9 hours, 12 hours, and 24 hours groups, and the inflammation model was successfully established; 4. Compared with the 0 hour group, the protein and mRNA expression levels of the endoplasmic reticulum stress pathway-related indexes in the LPS-stimulated 9 hours, 12 hours, and 24 hours groups increased significantly (P<0.01), which showed the time-dependence; 5. After adding the PERK inhibitor GSK2606414, the mRNA and protein expression levels of endoplasmic reticulum stress-related indicators in the PERK inhibitor group were significantly reduced compared with those in the LPS group (P<0.05); 6. The mRNA and protein expression levels of pro-inflammatory cytokines and the fluorescence intensity of ROS in the PERK inhibitor group were significantly reduced compared with those in the LPS group (P<0.01). Conclusion  Targeting PERK-mediated endoplasmic reticulum stress inhibits LPS-induced inflammatory responses in microglia. 

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells (OPCs).    Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5) (Rosa26-LSL-cOpn5) was generated using CRISPR/Cas9 technology. These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals. In this model, tamoxifen administration induces Cre-mediated recombination, leading to specific expression of cOpn5 in NG2-positive OPCs. The specificity and efficiency of cOpn5 expression in OPCs were confirmed by  immunofluorescent staining. Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470nm blue light.    Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifentreated NG2-CreERT;cOpn5 mice. Crucially, calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470nm blue light, indicating successful optogenetic activation.   Conclusion We have successfully generated and validated a novel transgenic mouse model (NG2-CreERT;cOpn5) that permits specific and inducible optogenetic activation of OPCs. This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system. 

Objective  To observe the morphology of the superficial, middle, and deep layers of the masseter muscle and related bony structures in the lateral facial region of adults through gross anatomy, and to probe into the effects of these muscle layers on the bony structures of the lateral facial region.   Methods  The bilateral masseter muscles of 12 adult cadavers were exposed, and the superficial, middle, and deep layers were separated and measured for muscle length, tendon length, and muscle belly length. After the masseter muscles were stripped, the total thickness was measured, and the mandible and zygomatic arch were exposed to measure the angle of the mandibular angle, thickness of the zygomatic arch, and width of the zygomatic arch. Observations were made of the masseter tuberosities, and statistical analysis was conducted on their interrelations.   Results  The zygomatic arch thickness was positively correlated with the length of superficial, middle and deep masseter muscles and the length of superficial and middle masseter belly (r_{superficial masseter length}=0.624, r_{middle masseter length}=0.787, r_{deep masseter length}=0.423, r_{superficial masseter belly length}=0.493, r_{middle masseter belly length}=0.548). The width of the zygomatic arch was positively correlated with the lengths of the superficial and middle muscle layers and the middle muscle belly length (r_{superficial masseter length}=0.527, r_{middle masseter length}=0.521, r_{middle masseter belly length}=0.437). The angle of the mandibular angle was only negatively correlated with the middle muscle belly length (r=-0.422). The tuberosities of the superficial and middle masseter muscles were not affected by the corresponding muscle layers; However, the tuberosity of the deep masseter was negatively correlated with the length of the deep muscle and the length of the deep tendon(r _{deep masseter length}=-0.543,r _{deep masseter tendon length}=-0.443).   Conclusion  In the masseter muscle layers of Chinese individuals, the superficial and middle layers have the most significant impact on the bony structures structures of the lateral facial region. These findings are of guiding significance for the remodeling of structures in the lateral facial region. 

 

Objective To investigate the differences of perineuronal net (PNN) and parvalbumin (PV)-positive neuron distribution across specific brain regions between young and aged mice.  Methods Brains from young (45 days) and aged (350 days) mice (n=4 per group) were fixed with 4% paraformaldehyde, sectioned (50 μm) using a vibratome, and stained with Wisteria floribunda agglutinin (WFA) and PV immunofluorescence. Quantitative analyses of PNN-positive and PV-positive neurons, along with PNN encapsulation of PV-positive neurons, were performed in the anterior cingulate cortex (ACC), somatosensory cortex barrel field layer 4 (S1BF L4), striatum (STR), and hippocampal CA2 region.    Results Aged mice exhibited no significant changes in PNN-positive or PV-positive neuron counts in ACC, S1BF L4, or STR compared to young mice, but showed significantly increased PNN encapsulation of PV-positive neurons. In hippocampal CA2, PNN-positive neurons increased significantly without PV-positive neuron alterations.    Conclusion The differences in PNN-PV neuron interactions and PNN density exist in specific brain regions of young and aged mice. 

Alzheimer’s disease (AD) is one of the most common degenerative diseases of the central nervous system in the elderly population, and genetic factors play an important role in its development. Microglia, as resident macrophages in the central nervous system, are closely related to the occurrence and development of AD. Human AD brain tissue staining result  and Genome-Wide Association Studies (GWAS) indicate that AD risk genes such as apolipoprotein E (APOE)4, triggering receptor expressed on myeloid cells 2 (TREM2), REV-ERBα and ATP binding cassette (ABC) family are involved in inducing lipid metabolism disorders in microglia and the occurrence of lipid-droplet-accumulating microglia (LDAM). This article reviews the genetic causes of LDAM, and discusses the possible mechanism of AD induced by neuronal damage and other means.

Objective To investigate the effects of remimazolam (REM) on cerebral ischemia-reperfusion injury (CIRI) rats and the AMP-activated protein kinase (AMPK)/NOD-like receptor protein 3 (NLRP3) signaling pathway. Methods  One hundred rats were selected to construct the CIRI rat model(Mod) and stochastically separated into a Mod group, low, medium, and high dose remifentanil groups (REM-L, REM-M, REM-H), and high dose remifentanil+pathway inhibitor Compound C group (REM-H+Compound C), with 20 rats in each group. Another 20 healthy rats were included as the control(Ctrl) group. All rats were subjected to neurobehavioral scoring. The water content, infarct area, and oxidative stress indicators of brain tissue were detected. The morphology and apoptosis of brain tissue were observed by HE and TUNEL staining. Western blotting was applied to detect protein expression related to the AMPK/NLRP3 signaling pathway. Results  Compared with the Mod group, with the increase of REM dose, the movement disorders in rats were alleviated, the overall structure of brain tissue gradually recovered, pathological damage was reduced, the area of cerebral infarction, brain water content, and apoptosis rate of brain tissue cells decreased, reactive oxygen species(ROS) level, malondialdehyde(MDA) content, and NLRP3 and Caspase-1 protein expression levels decreased, superoxide dismutase the(SOD) content and AMPK protein expression level increased (P<0.05). Compared with the REM-H group, the REM-H+Compound C group showed aggravated motor disorders, and more severe pathological damage to brain tissue, the area of cerebral infarction, cerebral water content and apoptosis rate of brain tissue cells increased, the ROS level, MDA content and the protein expression of NLRP3 and Caspase-1 increased, while the content of SOD and the protein expression decreased (P<0.05).   Conclusion  Remimazolam can enhance the antioxidant function of the body, reduce brain cell apoptosis, alleviate brain tissue injury, and thus have a certain protective effect on ischemia-reperfusion brain injury in rats, the mechanism of which may be related to the activation of the AMPK/NLRP3 signaling pathway.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1 (SOS1-IT1) affects enhancer of zeste homolog 2 (EZH2) protein expression in endometrial cancer cells Ishikawa and RL95-2.   Methods  Lentiviral transfection of short hairpin RNA(shRNA) and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1. The mechanism of EZH2 expression regulation was studied using Real-time PCR, Western blotting, and chromatin immunoprecipitation.  Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues. Knocking down SOS1-IT1 significantly reduces the expression of EZH2, inhibited the proliferation and migration of Ishikawa and RL95-2 cells, and could reduced the acetylation of histone H3 at position 27 (H3K27) and the enrichment of CREB binding protein (CBP) in the EZH2 gene promoter region. Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP. CBP could bind to SOS1-IT1 RNA, and this binding ability was weakened when CBP was knocked down. Conclusion   SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region, thereby affecting the proliferation and migration ability of endometrial cancer cells. 

Objective To investigate the anatomical and microscopic structures of interstitial fluid flow channels in the skin tissue of hand dorsum in human cadavers.  Methods  Totally 7 fresh cadavers within 12 hours post-mortem were included. MRI was used to observe the distribution of interstitial fluid flow from the first phalanx of the fingers to the wrist, precisely locating the flow channels. Based on imaging results, histological analyses were conducted to determine the histological characteristics of the flow channels. Furthermore, multi-immunofluorescence and microcomputed tomography (Micro-CT) techniques were employed to analyze the channels, and image post-processing was used to elucidate their anatomical structures at the microscopic level.   Results  After injecting a contrast agent into the first phalanx of ten finger specimens and applying repeated pressure, MRI image revealed centripetal long-range interstitial fluid flow along channels distinct from blood vessels and lymphatic vessels. Histological analysis and Micro-CT further confirmed that the flow primarily occurred within the fibrous connective tissue and adventitia of the skin.   Conclusion  The orderly fibrous connective tissue and adventitia in the skin form the interstitial fluid flow channels in the human hand dorsum skin, named as “stromal membrane channels” in the skin. 

 Objective To construct a predictive model for high-grade pathological components of early invasive lung adenocarcinoma(ILAC) based on radiomics.    Methods Collecting information on total 495 patients who underwent radical operation and were pathologically diagnosed as stage Ⅰ in the cardiothoracic surgery of Zhoushan Hospital from January 2015 to December 2019, including gender, age, pathological findings, tumor markers and preoperative chest CT images. The micropapillary and solid components in postoperative pathology were defined as “high-grade pathological components”, while those without high-grade pathological components were classified into the low-grade group and those with high-grade pathological components were classified into the high-grade group. And patients were randomly divided into the training set(343 cases) and the validation set(152 cases) with a ratio of 7∶3 using the simple randomization grouping method. The region of interest of nodules on CT images were delineated layer by layer by scientific research platform and 1950 radiomics features were extracted. And then those features were filtrated by Ftest, Pearson correlation coefficient, and L1 based feature selection. A model was built by using Logistic regression machine learning classifier, named mod 2, and radscore was also obtained. Differences between general information and CT features were analyzed. Binary Logistic regression analysis was used to construct a model for statistically significant variables, named mod 1. At the same time, Radscore was added to build the mod and named comb mod. The area under the curve(AUC), sensitivity and specificity of the three models were calculated. A nomogram was also drawn.   Results A total of 495 patients were divided into the training set (n=343) and the validation set (n=152). Gender, carcinoma embryonic antigen(CEA), nodule, and maximum diameter were screened out in clinical features and involved in constructing the mod 1. Twelve features were selected from the radiomics features to build mod 2. Comb mod performed best, training set AUC:0.887, validation set AUC:0.875, and had good clinical practicability.    Conclusion The model composed of general feature, CT feature and radiomics features could accurately predict high-grade pathological components in early ILAC, and provide references for clinicians to choose surgical method  for patients. 

Objective To explore the epidemiological characteristics and magnetic resonance angiography (MRA) features of duplicated and accessory middle cerebral artery (DMCA and AMCA), and to raise awareness of this vascular variation.

 Methods  Imaging data of 8131 patients underwent cranial MRI and MRA examinations in Anyang People’s Hospital from April 2023 to August 2023 were collected, and DMCA or AMCA variation were investigated. The epidemiological characteristics, MRA features and classification of DMCA and AMCA were analyzed. Meanwhile the concurrent other cerebrovascular variations were observed. Results  Totally 113 of 8131 patients were detected to have 119 DMCA or AMCA vascular variants. There were 64 DMCA including 24 type A and 40 type B, and there were 55 AMCA including 38 of type 1 and 17 of type 2. The relative diameter of type A DMCA was larger than that of type B DMCA, type 1 and type 2 AMCA. The difference was statistically significant(P<0.05). The incidence of DMCA and AMCA combined with other cerebrovascular variations was 54.69% and 34.69%, respectively.   Conclusion  MRA is simple and practicable, and can intuitively display DMCA or AMCA. So, it can be used as an important method  for the diagnostic of DMCA or AMCA. The DMCA and AMCA variation make related surgeries more complex, and it plays an undeniable role in the prognosis of related cerebral infarction. This vascular variation has important clinical significance for guiding neurosurgeons and neurologists to formulate reasonable treatment plans.

Objective To investigate the potential mechanism of action of polygonatum odoratum in treating Alzheimer’s disease through the utilization of network pharmacology and molecular docking techniques.    Methods The methods employed include target screening, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking simulations to assess the binding interactions between the active compounds in polygonatum odoratum (POD) and the key target proteins associated with Alzheimer’s disease. Subsequently, lipopolysaccharide（LPS）was used to induce an inflammatory cell model in BV2 microglial cells. After treating the cell model with POD extract for 24 hours, the cells were collected, and the expression of the target genes were detected by Real-time PCR.    Results Eight active ingredients and 172 targets of POD were screened. The biological processes such as protein phosphorylation and signal transduction, protein binding and ATP binding were obtained by GO functional analysis. KEGG enrichment yielded PI3K/Akt, cAMP and other signaling pathways. The molecular docking result  showed that the active ingredient of POD had well binding activity with epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC), tumor necrosis factor （TNF）, STAT3. Through Real-time PCR experiments, the gene expressions of inducible nitric oxide synthase (iNOS), prostaglandin G/H synthase 2(PTGS2), interleukin (IL) -6, and IL-1β in the LPS-induced inflammatory cell model were significantly upregulated. After treating the inflammatory model with POD extract for 24 hours, the expression of TNF-α was significantly reduced, the expression of STAT3 was upregulated, there were no significant changes in the expressions of SRC and EGFR.    Conclusion Network pharmacology suggests polygonatum odoratum’s potential anti-Alzheimer’s effects may be mediated through its interaction with targets such as EGFR, TNF, SRC, and STAT3. The experimental results  suggest that polygonatum odoratum exerts an anti-inflammatory effect by acting on TNF-α, which may further alleviate the symptoms of Alzheimer’s disease. 

Objective To develop the application technology of finger length ratios in the selection of Muay Thai athletes, and to provide practical guidance for improving the competitive level of Muay Thai.    Methods By using the method  of snowball sampling and simple random sampling,413 subjects were selected in Bangkok, Thailand, including 84 male Muay Thai professional players, 62 female Muay Thai professional players, 137 ordinary male college students and 130 female college students. The finger length of the subjects was measured and their finger length ratios was calculated. SPSS 20.0 statistical software was used for discriminant analysis.    Results The 2D∶3D, 2D∶4D, 2D∶5D,3D∶4D and  3D∶5D of male Muay Thai professional players were significantly lower than that in the general male Thai population, and the 2D∶4D, 3D∶4D and 3D∶5D of female Muay Thai players were significantly lower than that in the general female Thai population, and the above differences were statistically significant (P<0.05). Discriminant functions developed using both the full model and stepwise method  were statistically significant, demonstrating high accuracy and stability. The correct discrimination rates were higher in the male population than that in the female population.When distinguishing between Muay Thai professional fighters and the general Thai population, the optimal 2D∶4D threshold for males is 0.951, and for females, it was 0.960.    Conclusion The discriminant model of Muay Thai professional players and ordinary people based on the ratios of finger length can provide important reference for the selection of Muay Thai athletes. 

Objective  To investigate the effect of farrerol on pyroptosis induced by hydrogen peroxide (H₂O₂) in lens epithelial cells through regulating JAK2/STAT3 signaling pathway.   Methods  Thirty-six neonatal SD rats were randomly divided into normal group, cataract group (20 μmol/kg sodium selenite), farrerol low dose, medium dose and high dose groups (10, 20, 40 mg/kg farrerol) and positive control group (benzyda lysine eye drops). Lens turbidity was observed by slit-lamp and scored, and pathological changes of lens were observed by HE staining. Human lens epithelial cells were cultured and divided into control group, model group, low concentration farrerol group (20 mg/L), high concentration farrerol group (40 mg/L), high concentration farrerol+R08191 group (40 mg/L+10 μmol/L), except the control group, other groups were induced by H₂O₂. The cell activity was detected by CCK-8 method ; the concentrations of interleukin(IL-1β) and IL-18 in cell culture medium were measured by ELISA; inverted phase contrast microscope was used to observe the cell scorch in each group; The expression of N-terminal fragment of GSDMD(GSDMD-N) protein was detected by immunofluorescent staining; the content of reactive ozygen species(ROS) was measured by flow cytometry; the expressions of latent heat protein(NLRP3), apoptosis-associate speck-like protein containing a CARD(ASC), Caspase1, GSDMD-N, JAK2/STAT3 pathway proteins were detected by Western blotting.   Results  In cataract rats, the lens epithelial cells were disorderly and loosely arranged, the lens fibrosis/liquefaction, and the lens turbidity score increased (P<0.05). Compared with the cataract group, the lens damage and the lens turbidity score decreased in the low, medium and farrerol high dose group and the positive control group (P<0.05), and the effect of the farrerol high dose group was the best, which was basically consistent with the positive control group. The cells in the control group were closely connected and arranged in order, without scorched cells; in the model group, the cells were swollen and had typical charring characteristics of bubble like protrusion; Compared with the model group, the cell bubble protrusion in the low concentration farrerol group and the high concentration farrerol group was alleviated; Compared with the high concentration farrerol group, the cell bubble protrusion in the high concentration farrerol +R08191 group was aggravated. Compared with the control group, the cell survival rate in model group was decreased, the levels of IL-18 and IL-1β in supernatant, the number of GSDMD-N positive cells, the level of ROS, the expression of NLPR3, ASC, Caspase1, GSDMD-N protein, p-JAK2/JAK2,  p-STAT3/STAT3 were increased (P<0.05); Compared with the model group, the cell survival rate in the low concentration farrerol group and the high concentration farrerol group was increased, the levels of IL-18 and IL-1β in supernatant, the number of GSDMD-N positive cells, the level of ROS, the expression of NLPR3, ASC, Caspase-1, GSDMD-N protein, p-JAK2/JAK2, p-STAT3/STAT3 were decreased (P<0.05); compared with the high concentration farrerol group, the cell survival rate in the high concentration farrerol+R08191 group was decreased, the levels of IL-18 and IL-1β in supernatant, the number of GSDMD-N positive cells, the level of ROS, the expression of NLPR3, ASC, Caspase-1, GSDMD-N protein, p-JAK2/JAK2, p-STAT3/STAT3 signaling were increased (P<0.05).   Conclusion  Farrerol may inhibit H₂O₂-induced pyroptosis of lens epithelial cells by inhibiting JAK2/STAT3 signaling pathway.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2) in spinal motor neuron degeneration in amyotrophic lateral sclerosis (ALS).   Methods   Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1) mutant ALS transgenic mice. hSOD1G93A mutant ALS transgenic mice were selected for animal experimental validation, with littermate wild type(WT) mice serving as the control group. A total of 36 pairs were divided into four groups, namely the pre-onset stage, early-onset stage, mid-onset stage, and late-onset stage. The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR, Western blotting and immunofluorescent double-label staining. The hSOD1G93A mutant NSC34 motor neuron-like cell model was established, and in vitro experiments were carried out to detect the changes in srGAP2 expression, and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.   Results  Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS  mice. Animal experiments verified that compared with the WT mice, the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset, mid-onset and late-onset stages. Compared with the WT mice, srGAP2 integral absorbance (IA) values in srGAP2⁺/NeuN⁺ double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower, srGAP2 IA values in srGAP2⁺/GFAP⁺ double-positive cells were higher; Compared with the hSOD1WT NSC34 cells, the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells. Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells, and up-regulated the expression level of synapse-related protein βⅢ-tubulin and growth associated protein 43（GAP43）.   Conclusion   Low expression of srGAP2 is closely associated with the progression of ALS, while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS. 

 Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson’s disease(PD) through fecal microbiota transplantation.   Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Fecal microbiota from both the model group and the curcumin(Cur)-treated group (80 mg/kg) were collected and analyzed. The experiment involving fecal microbiota transplantation was structured into four distinct groups, fecal microbiota solvent transplantation group (FMTcon), model fecal microbiota transplantation group (FMTmodel), MPTP-induced model group (model), and model group subjected to fecal microbiota transplantation following curcumin treatment (model+FMTCur). The motor skills of the mice were assessed by using rod rotation, pole climbing experiment, and open field tests. Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase (TH)-positive neurons in the substantia nigra of the brain. Additionally, the gene expression of tumor necrosis factor-α (TNF-α) in the midbrain of mice was analyzed, alongside the protein expression of nuclear factor-κB(NF-κB) and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3).   Results The subacute PD animal model in mice was successfully established, and fecal microbiota were separated and gathered. The model group exhibited significant motor impairment, as evidenced by a shortened rod rotation time (P<0.05), prolonged pole climbing time (P<0.05), significantly reduced total movement distance within the open field (P<0.001), and decreased time spent in the central zone (P<0.01). The relative expression level of TH+ neurons in the substantia nigra was significantly reduced (P<0.01). Moreover, mRNA expression of TNF-α in the midbrain increased significantly(P<0.01), along with significant elevations in protein expression of NF-κB (P<0.001), phosphorylated NF-κB (p-NF-κB) (P<0.01), NLRP3 (P<0.001), and Caspase-1 (P<0.01).The transplanted model microbial group (FMTmodel) also exhibited motor impairment, manifested by a trend of shortened rod rotation time, prolonged pole climbing time, a significant decrease in total movement distance within the open field (P<0.01), and a trend of shortened time spent in the central zone. The relative expression level of TH⁺ neurons in the substantia nigra decreased significantly(P<0.05). Additionally, mRNA expression of TNF-α in the midbrain increased significantly(P<0.01), along with notable elevations in the protein expression of NF-κB (P<0.05), and Caspase-1 (P<0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice (model+FMTCur) showed improvements in motor abilities, evidenced by shortened pole climbing time (P<0.05), significantly prolonged rod rotation time (P<0.01), and extended time spent in the central zone (P<0.05). The relative expression level of TH+ dopaminergic neurons in the substantia nigra increased significantly(P<0.05). Moreover, mRNA expression of TNF-α in the midbrain decreased significantly(P<0.01), along with notable reductions in the protein expression of NF-κB (P<0.001), p-NF-κB (P<0.01), NLRP3 (P<0.05), and Caspase-1 (P<0.01).   Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits, damage TH+ neurons in the substantia nigra, and trigger neuroinflammation in the brain. Subsequent curcumin treatment can ameliorate these deficits, reverse damage to TH+ neurons, reduce neuroinflammatory factors, and decrease the expression of NF-κB and NLRP3 pathways. This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota. 

Objective To investigate the expressions of annexin A2 and glycogen synthesis kinase-3β (GSK-3β) in cutaneous squamous cell carcinoma (CSCC) tissues, and to analyze their correlation with CSCC as well as their clinical pathological diagnostic value.   Methods  The pathological tissues of 68 patients with CSCC and 40 patients with keratoacanthoma (KA) who underwent surgical treatment in the Department of Dermatology of the Second Hospital of Nanning from October 2020 to May 2024 were collected, and the surrounding normal skin tissues of 32 patients with benign skin diseases were used as controls. The expressions of annexin A2, GSK-3β and β-catenin were detected by immunohistochemistry and Western blotting. Spearman was used to evaluate the correlation between the expressions of annexin A2 and GSK-3β and the pathological characteristics in CSCC. The receiver operating characteristic (ROC) curve was drawn to analyze the clinical diagnostic value of annexin A2 and GSK-3β in CSCC.  Results Compared with the normal skin tissues, the expressions of annexin A2 and βcatenin in CSCC increased, and GSK-3β  decreased (P<0.05); Compared with the KA tissues, the expression of annexin A2 in CSCC tissues increased (P<0.05). The expression of annexin A2 was negatively correlated with that of GSK-3β in CSCC (r=-0.3901, P<0.01). GSK-3β expression was related to tissue differentiation, with lower expression in poorly differentiated patients’ cancer tissues (P<0.05). The sensitivity of annexin A2 and GSK-3β for diagnosis of CSCC was 85.3% and 41.2%, respectively, with specificities of 46.9% and 84.4% respectively. The sensitivity of annexin A2 for distinguishing between CSCC and KA was 85.3%, with a specificity of 40.0%.   Conclusion  Annexin A2 and GSK-3β may be used as potential biomarkers for the early diagnosis or differential diagnosis of CSCC, and play important roles in the development of CSCC. Their mechanism may be related to the activation of Wnt/β-catenin signaling pathway. 

 Objective  To analyze the relationship between obesity indicators，muscle mass indices and hypertension in Dongxiang adults, and establish and evaluate a Nomogram model based on these indicators used to predict the risk of hypertension in this population.    Methods  A total of 1209 Dongxiang adults from Linxia Prefecture, Gansu Province were selected, 11 obesity indicators and 5 muscle mass indicators，including neck circumference (NC), waist-to-hip ratio (WHR), BMI, ponderal index (PI), conicity index (CI), a body shape index (ABSI), body roundness index (BRI), abdominal volume index (AVI), hip index (HI), body adiposity index (BAI), and the ratio of limb fat mass to body weight(LFWR), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), appendicular skeletal muscle mass to BMI ratio (ASMBMI), skeletal muscle index (SMI), and trunk muscle mass to body weight ratio(TMWR) were measured. Logistic regression analysis was used to explore the relationship between each indicator and hypertension. Nomogram prediction model was constructed and validated by using R language.   Results Among Dongxiang males, the NC, BMI, PI, WHR, CI, AVI, BRI, BAI, ASM, ASMI, and LFWR were lower in the normal and highnormal blood pressure groups compared to the hypertensive group, while SMI, ASMBMI, and TMWR were higher. Among females, similar trends were observed, with lower NC, BMI, PI, WHR, CI, AVI, BRI, BAI, and LFWR in the normal blood pressure and high-normal blood pressure groups compared to the hypertensive group, but SMI, ASMBMI, and TMWR higher than the hypertensive group (P<0.05). Results of multivariate Logistic regression analysis indicated that age, NC, and WHR were risk factors for hypertension in Dongxiang adults, while was protective factor (P<0.05). The area under curve(AUC) of the Nomogram model constructed based on these factors was 0.796, and the Bootstrap internal validation C-index was 0.7957, indicating good calibration of the model.    Conclusion  The Nomogram model constructed based on obesity and muscle mass indicators has good predictive efficiency for predicting the risk of hypertension in Dongxiang adults. 

 Objective  To explore the relationship between NANOS3 and P-bodies in oocytes and the mechanism of their interaction during early oogenesis.  Methods  The co-localization of NANOS3 and dead box helicase 6(DDX6) in day post postnatal 1 (1dpp) mouse oocytes was observed by immunofluorescence, and the interaction between NANOS3 and DDX6 was detected by immunoprecipitation. NANOS3 and DDX6 full-length plasmids were constructed to transfect HEK293T cells, and the mechanism of their interaction was investigated by immunofluorescence and immunoprecipitation. NANOS3 transfected HeLa cells to investigate whether NANOS3 had the ability of liquid-liquid phase separation (LLPS) by live-cell imaging. The proteins recruited by P-bodies in early oogenesis were identified by DDX6-immunoprecipitation-mass spectrometry(DDX6-IP-MS).    Results  NANOS3 and DDX6 colocalized and interacted with each other in 1dpp mouse oocytes. However, the co-localization of NANOS3 and DDX6 was not observed in HEK293T cells that had been transfected, but co-immunoprecipitation still demonstrated an interaction between these two proteins. Besides, live-cell imaging revealed that NANOS3 exhibited dynamic fluid-like properties within cells, which may promote the formation of P-bodies through LLPS. Finally, DDX6-IP-MS revealed that DDX6 might recruit NANOS3 into P-bodies by binding to the NANOS3 interacting protein Pumilio.   Conclusion  NANOS3 serves as a specific component of P-bodies in neonatal oocytes and may be involved in the regulation of early oogenesis.